CA3225091A1 - Animaux porteurs des sequences c5 et c3 humanisees - Google Patents
Animaux porteurs des sequences c5 et c3 humanisees Download PDFInfo
- Publication number
- CA3225091A1 CA3225091A1 CA3225091A CA3225091A CA3225091A1 CA 3225091 A1 CA3225091 A1 CA 3225091A1 CA 3225091 A CA3225091 A CA 3225091A CA 3225091 A CA3225091 A CA 3225091A CA 3225091 A1 CA3225091 A1 CA 3225091A1
- Authority
- CA
- Canada
- Prior art keywords
- rodent
- human
- mouse
- protein
- gene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 241001465754 Metazoa Species 0.000 title abstract description 28
- 241000283984 Rodentia Species 0.000 claims abstract description 327
- 101100440311 Homo sapiens C5 gene Proteins 0.000 claims abstract description 85
- 238000000034 method Methods 0.000 claims abstract description 68
- 230000001105 regulatory effect Effects 0.000 claims abstract description 64
- 101000901154 Homo sapiens Complement C3 Proteins 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 52
- 102000057770 human C3 Human genes 0.000 claims abstract description 42
- 101150069146 C5 gene Proteins 0.000 claims abstract description 36
- 101150071258 C3 gene Proteins 0.000 claims abstract description 32
- 150000007523 nucleic acids Chemical group 0.000 claims abstract description 24
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 302
- 102000004169 proteins and genes Human genes 0.000 claims description 145
- 210000002966 serum Anatomy 0.000 claims description 93
- 230000024203 complement activation Effects 0.000 claims description 75
- 108700024394 Exon Proteins 0.000 claims description 57
- 230000000295 complement effect Effects 0.000 claims description 52
- 101100328540 Homo sapiens C3 gene Proteins 0.000 claims description 47
- 101100328542 Mus musculus C3 gene Proteins 0.000 claims description 44
- 238000003556 assay Methods 0.000 claims description 31
- 101100440312 Mus musculus C5 gene Proteins 0.000 claims description 30
- 101710131943 40S ribosomal protein S3a Proteins 0.000 claims description 29
- 230000014509 gene expression Effects 0.000 claims description 23
- 108020004707 nucleic acids Proteins 0.000 claims description 15
- 102000039446 nucleic acids Human genes 0.000 claims description 15
- -1 small molecule chemical compound Chemical class 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 230000003247 decreasing effect Effects 0.000 claims description 4
- 238000011577 humanized mouse model Methods 0.000 claims description 4
- 238000007423 screening assay Methods 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 abstract description 66
- 241000700159 Rattus Species 0.000 abstract description 59
- 230000004154 complement system Effects 0.000 abstract description 22
- 241000699666 Mus <mouse, genus> Species 0.000 description 195
- 235000018102 proteins Nutrition 0.000 description 132
- 210000004027 cell Anatomy 0.000 description 54
- 230000002949 hemolytic effect Effects 0.000 description 39
- 108090000765 processed proteins & peptides Proteins 0.000 description 30
- 102000004196 processed proteins & peptides Human genes 0.000 description 30
- 235000001014 amino acid Nutrition 0.000 description 29
- 229920001184 polypeptide Polymers 0.000 description 26
- 230000001225 therapeutic effect Effects 0.000 description 24
- 108700028369 Alleles Proteins 0.000 description 22
- 150000001413 amino acids Chemical class 0.000 description 21
- 239000000523 sample Substances 0.000 description 21
- 241001529936 Murinae Species 0.000 description 19
- 241000894007 species Species 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 18
- 102000000989 Complement System Proteins Human genes 0.000 description 17
- 108010069112 Complement System Proteins Proteins 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- 108091034117 Oligonucleotide Proteins 0.000 description 16
- 230000006870 function Effects 0.000 description 16
- 238000011144 upstream manufacturing Methods 0.000 description 16
- 239000002773 nucleotide Substances 0.000 description 15
- 125000003729 nucleotide group Chemical group 0.000 description 15
- 108700019146 Transgenes Proteins 0.000 description 14
- 230000003285 pharmacodynamic effect Effects 0.000 description 13
- 230000002441 reversible effect Effects 0.000 description 13
- 239000012634 fragment Substances 0.000 description 12
- 210000001161 mammalian embryo Anatomy 0.000 description 12
- 150000003384 small molecules Chemical class 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 206010018910 Haemolysis Diseases 0.000 description 10
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 10
- 125000003275 alpha amino acid group Chemical group 0.000 description 10
- 239000005557 antagonist Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 230000037361 pathway Effects 0.000 description 10
- 108091026890 Coding region Proteins 0.000 description 9
- 102100022133 Complement C3 Human genes 0.000 description 9
- 102100031506 Complement C5 Human genes 0.000 description 9
- 230000004913 activation Effects 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000008588 hemolysis Effects 0.000 description 9
- 238000011813 knockout mouse model Methods 0.000 description 9
- 241000124008 Mammalia Species 0.000 description 8
- 108091036066 Three prime untranslated region Proteins 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 238000011529 RT qPCR Methods 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 210000004602 germ cell Anatomy 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000000349 chromosome Anatomy 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 239000007790 solid phase Substances 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 230000009261 transgenic effect Effects 0.000 description 6
- 206010063837 Reperfusion injury Diseases 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 238000001212 derivatisation Methods 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000000770 proinflammatory effect Effects 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- 238000006352 cycloaddition reaction Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000012239 gene modification Methods 0.000 description 4
- 230000005017 genetic modification Effects 0.000 description 4
- 235000013617 genetically modified food Nutrition 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- 238000011740 C57BL/6 mouse Methods 0.000 description 3
- 108010028773 Complement C5 Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 3
- 206010064930 age-related macular degeneration Diseases 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 210000002257 embryonic structure Anatomy 0.000 description 3
- 238000003205 genotyping method Methods 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 208000002780 macular degeneration Diseases 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002207 retinal effect Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- RFLVMTUMFYRZCB-UHFFFAOYSA-N 1-methylguanine Chemical compound O=C1N(C)C(N)=NC2=C1N=CN2 RFLVMTUMFYRZCB-UHFFFAOYSA-N 0.000 description 2
- YSAJFXWTVFGPAX-UHFFFAOYSA-N 2-[(2,4-dioxo-1h-pyrimidin-5-yl)oxy]acetic acid Chemical compound OC(=O)COC1=CNC(=O)NC1=O YSAJFXWTVFGPAX-UHFFFAOYSA-N 0.000 description 2
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 description 2
- XDNDSAQVXNZKGP-UHFFFAOYSA-N 3-(1h-pyrrol-2-yl)propanoic acid Chemical compound OC(=O)CCC1=CC=CN1 XDNDSAQVXNZKGP-UHFFFAOYSA-N 0.000 description 2
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 description 2
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
- ZLAQATDNGLKIEV-UHFFFAOYSA-N 5-methyl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CC1=CNC(=S)NC1=O ZLAQATDNGLKIEV-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 102400000069 Activation peptide Human genes 0.000 description 2
- 101800001401 Activation peptide Proteins 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 2
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 108010028780 Complement C3 Proteins 0.000 description 2
- 108010034753 Complement Membrane Attack Complex Proteins 0.000 description 2
- 241000252212 Danio rerio Species 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 2
- 229930010555 Inosine Natural products 0.000 description 2
- 241000282560 Macaca mulatta Species 0.000 description 2
- HYVABZIGRDEKCD-UHFFFAOYSA-N N(6)-dimethylallyladenine Chemical compound CC(C)=CCNC1=NC=NC2=C1N=CN2 HYVABZIGRDEKCD-UHFFFAOYSA-N 0.000 description 2
- 108091092724 Noncoding DNA Proteins 0.000 description 2
- 206010030043 Ocular hypertension Diseases 0.000 description 2
- 208000030768 Optic nerve injury Diseases 0.000 description 2
- 241000282577 Pan troglodytes Species 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 206010038997 Retroviral infections Diseases 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 210000002459 blastocyst Anatomy 0.000 description 2
- 210000001109 blastomere Anatomy 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical class SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 208000004264 complement component 5 deficiency Diseases 0.000 description 2
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229960003786 inosine Drugs 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- DRAVOWXCEBXPTN-UHFFFAOYSA-N isoguanine Chemical compound NC1=NC(=O)NC2=C1NC=N2 DRAVOWXCEBXPTN-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000003016 pheromone Substances 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 229940076372 protein antagonist Drugs 0.000 description 2
- 150000007660 quinolones Chemical class 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 150000003548 thiazolidines Chemical class 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- CADQNXRGRFJSQY-UOWFLXDJSA-N (2r,3r,4r)-2-fluoro-2,3,4,5-tetrahydroxypentanal Chemical compound OC[C@@H](O)[C@@H](O)[C@@](O)(F)C=O CADQNXRGRFJSQY-UOWFLXDJSA-N 0.000 description 1
- WJNGQIYEQLPJMN-IOSLPCCCSA-N 1-methylinosine Chemical compound C1=NC=2C(=O)N(C)C=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O WJNGQIYEQLPJMN-IOSLPCCCSA-N 0.000 description 1
- 238000011714 129 mouse Methods 0.000 description 1
- HLYBTPMYFWWNJN-UHFFFAOYSA-N 2-(2,4-dioxo-1h-pyrimidin-5-yl)-2-hydroxyacetic acid Chemical compound OC(=O)C(O)C1=CNC(=O)NC1=O HLYBTPMYFWWNJN-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- ZUYKJZQOPXDNOK-UHFFFAOYSA-N 2-(ethylamino)-2-thiophen-2-ylcyclohexan-1-one;hydrochloride Chemical class Cl.C=1C=CSC=1C1(NCC)CCCCC1=O ZUYKJZQOPXDNOK-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- SGAKLDIYNFXTCK-UHFFFAOYSA-N 2-[(2,4-dioxo-1h-pyrimidin-5-yl)methylamino]acetic acid Chemical compound OC(=O)CNCC1=CNC(=O)NC1=O SGAKLDIYNFXTCK-UHFFFAOYSA-N 0.000 description 1
- XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical compound NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 description 1
- XMSMHKMPBNTBOD-UHFFFAOYSA-N 2-dimethylamino-6-hydroxypurine Chemical compound N1C(N(C)C)=NC(=O)C2=C1N=CN2 XMSMHKMPBNTBOD-UHFFFAOYSA-N 0.000 description 1
- SMADWRYCYBUIKH-UHFFFAOYSA-N 2-methyl-7h-purin-6-amine Chemical compound CC1=NC(N)=C2NC=NC2=N1 SMADWRYCYBUIKH-UHFFFAOYSA-N 0.000 description 1
- KOLPWZCZXAMXKS-UHFFFAOYSA-N 3-methylcytosine Chemical compound CN1C(N)=CC=NC1=O KOLPWZCZXAMXKS-UHFFFAOYSA-N 0.000 description 1
- GJAKJCICANKRFD-UHFFFAOYSA-N 4-acetyl-4-amino-1,3-dihydropyrimidin-2-one Chemical compound CC(=O)C1(N)NC(=O)NC=C1 GJAKJCICANKRFD-UHFFFAOYSA-N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 description 1
- VKLFQTYNHLDMDP-PNHWDRBUSA-N 5-carboxymethylaminomethyl-2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C(CNCC(O)=O)=C1 VKLFQTYNHLDMDP-PNHWDRBUSA-N 0.000 description 1
- ZFTBZKVVGZNMJR-UHFFFAOYSA-N 5-chlorouracil Chemical compound ClC1=CNC(=O)NC1=O ZFTBZKVVGZNMJR-UHFFFAOYSA-N 0.000 description 1
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 1
- KELXHQACBIUYSE-UHFFFAOYSA-N 5-methoxy-1h-pyrimidine-2,4-dione Chemical compound COC1=CNC(=O)NC1=O KELXHQACBIUYSE-UHFFFAOYSA-N 0.000 description 1
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 1
- DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 description 1
- XTPUXCVIDQFHIT-UHFFFAOYSA-N 8-(3-methylbut-3-enyl)-2-methylsulfanyl-7h-purin-6-amine Chemical compound CSC1=NC(N)=C2NC(CCC(C)=C)=NC2=N1 XTPUXCVIDQFHIT-UHFFFAOYSA-N 0.000 description 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 208000010370 Adenoviridae Infections Diseases 0.000 description 1
- 206010060931 Adenovirus infection Diseases 0.000 description 1
- 206010052613 Allergic bronchitis Diseases 0.000 description 1
- 102000013918 Apolipoproteins E Human genes 0.000 description 1
- 108010025628 Apolipoproteins E Proteins 0.000 description 1
- 206010003557 Asthma exercise induced Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000219495 Betulaceae Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006474 Bronchopulmonary aspergillosis allergic Diseases 0.000 description 1
- 101150114997 CD59 gene Proteins 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000016918 Complement C3 Human genes 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000191823 Cynomys Species 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- ZAQJHHRNXZUBTE-WUJLRWPWSA-N D-xylulose Chemical compound OC[C@@H](O)[C@H](O)C(=O)CO ZAQJHHRNXZUBTE-WUJLRWPWSA-N 0.000 description 1
- 238000011765 DBA/2 mouse Methods 0.000 description 1
- 238000011767 DBA/2J (JAX™ mouse strain) Methods 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 102100023387 Endoribonuclease Dicer Human genes 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 241001481760 Erethizon dorsatum Species 0.000 description 1
- 208000004657 Exercise-Induced Asthma Diseases 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 238000007341 Heck reaction Methods 0.000 description 1
- 108010006464 Hemolysin Proteins Proteins 0.000 description 1
- 238000006842 Henry reaction Methods 0.000 description 1
- 101000882982 Homo sapiens CDK5 regulatory subunit-associated protein 3 Proteins 0.000 description 1
- 101000907904 Homo sapiens Endoribonuclease Dicer Proteins 0.000 description 1
- 101001051093 Homo sapiens Low-density lipoprotein receptor Proteins 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- 206010048643 Hypereosinophilic syndrome Diseases 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 206010022680 Intestinal ischaemia Diseases 0.000 description 1
- 206010022822 Intravascular haemolysis Diseases 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- 101150088352 MDM1 gene Proteins 0.000 description 1
- 208000004451 Membranoproliferative Glomerulonephritis Diseases 0.000 description 1
- 235000011779 Menyanthes trifoliata Nutrition 0.000 description 1
- 240000008821 Menyanthes trifoliata Species 0.000 description 1
- 238000006957 Michael reaction Methods 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- SGSSKEDGVONRGC-UHFFFAOYSA-N N(2)-methylguanine Chemical compound O=C1NC(NC)=NC2=C1N=CN2 SGSSKEDGVONRGC-UHFFFAOYSA-N 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 208000016999 Parasitic Lung disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000035415 Reinfection Diseases 0.000 description 1
- 206010061481 Renal injury Diseases 0.000 description 1
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
- 241000725643 Respiratory syncytial virus Species 0.000 description 1
- 241000555745 Sciuridae Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- 238000006281 Stork reaction Methods 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 208000011589 adenoviridae infectious disease Diseases 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000010085 airway hyperresponsiveness Effects 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 238000005882 aldol condensation reaction Methods 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000006778 allergic bronchopulmonary aspergillosis Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 150000008378 aryl ethers Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 125000005228 aryl sulfonate group Chemical group 0.000 description 1
- 150000001541 aziridines Chemical class 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 238000007193 benzoin condensation reaction Methods 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical class C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000007675 cardiac surgery Methods 0.000 description 1
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 201000004897 cough variant asthma Diseases 0.000 description 1
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 208000022401 dense deposit disease Diseases 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 238000007878 drug screening assay Methods 0.000 description 1
- 208000011325 dry age related macular degeneration Diseases 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000007337 electrophilic addition reaction Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 201000009580 eosinophilic pneumonia Diseases 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 208000024695 exercise-induced bronchoconstriction Diseases 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 201000001505 hemoglobinuria Diseases 0.000 description 1
- 239000003228 hemolysin Substances 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 102000049790 human CDK5RAP3 Human genes 0.000 description 1
- 150000001469 hydantoins Chemical class 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002547 isoxazolines Chemical class 0.000 description 1
- 208000037806 kidney injury Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- IZAGSTRIDUNNOY-UHFFFAOYSA-N methyl 2-[(2,4-dioxo-1h-pyrimidin-5-yl)oxy]acetate Chemical compound COC(=O)COC1=CNC(=O)NC1=O IZAGSTRIDUNNOY-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 208000007892 occupational asthma Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 150000002917 oxazolidines Chemical class 0.000 description 1
- 150000002918 oxazolines Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- UKIUSKWWNRYHOO-UHFFFAOYSA-N pent-1-yn-1-ol Chemical compound CCCC#CO UKIUSKWWNRYHOO-UHFFFAOYSA-N 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 238000002732 pharmacokinetic assay Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 230000008832 photodamage Effects 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 208000036273 reactive airway disease Diseases 0.000 description 1
- 230000001603 reducing effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 150000007659 semicarbazones Chemical class 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 101150062190 sod1 gene Proteins 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 150000003549 thiazolines Chemical class 0.000 description 1
- 150000003555 thioacetals Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 150000003606 tin compounds Chemical class 0.000 description 1
- 230000030968 tissue homeostasis Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 230000009452 underexpressoin Effects 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- WCNMEQDMUYVWMJ-JPZHCBQBSA-N wybutoxosine Chemical compound C1=NC=2C(=O)N3C(CC([C@H](NC(=O)OC)C(=O)OC)OO)=C(C)N=C3N(C)C=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O WCNMEQDMUYVWMJ-JPZHCBQBSA-N 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 210000004340 zona pellucida Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
- A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/472—Complement proteins, e.g. anaphylatoxin, C3a, C5a
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/15—Humanized animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/035—Animal model for multifactorial diseases
- A01K2267/0368—Animal model for inflammation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4716—Complement proteins, e.g. anaphylatoxin, C3a, C5a
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Environmental Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Organic Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Pathology (AREA)
- Molecular Biology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Endocrinology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Plant Pathology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Food Science & Technology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461988581P | 2014-05-05 | 2014-05-05 | |
| US61/988,581 | 2014-05-05 | ||
| US201462067836P | 2014-10-23 | 2014-10-23 | |
| US62/067,836 | 2014-10-23 | ||
| CA2946412A CA2946412C (fr) | 2014-05-05 | 2015-05-04 | Animaux porteurs des sequences c5 et c3 humanisees |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2946412A Division CA2946412C (fr) | 2014-05-05 | 2015-05-04 | Animaux porteurs des sequences c5 et c3 humanisees |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3225091A1 true CA3225091A1 (fr) | 2015-11-12 |
Family
ID=53177902
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2946412A Active CA2946412C (fr) | 2014-05-05 | 2015-05-04 | Animaux porteurs des sequences c5 et c3 humanisees |
| CA3225091A Pending CA3225091A1 (fr) | 2014-05-05 | 2015-05-04 | Animaux porteurs des sequences c5 et c3 humanisees |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2946412A Active CA2946412C (fr) | 2014-05-05 | 2015-05-04 | Animaux porteurs des sequences c5 et c3 humanisees |
Country Status (15)
| Country | Link |
|---|---|
| US (5) | US9795121B2 (fr) |
| EP (3) | EP4317445A3 (fr) |
| JP (1) | JP6598798B2 (fr) |
| KR (1) | KR102461511B1 (fr) |
| CN (1) | CN106659146B (fr) |
| AU (1) | AU2015256299C1 (fr) |
| BR (1) | BR112016025751A2 (fr) |
| CA (2) | CA2946412C (fr) |
| ES (2) | ES2968749T3 (fr) |
| IL (1) | IL248481B (fr) |
| MA (1) | MA51519A (fr) |
| MX (1) | MX2016014504A (fr) |
| RU (2) | RU2713327C2 (fr) |
| SG (2) | SG10202003996YA (fr) |
| WO (1) | WO2015171523A1 (fr) |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR095196A1 (es) | 2013-03-15 | 2015-09-30 | Regeneron Pharma | Medio de cultivo celular libre de suero |
| MA51519A (fr) | 2014-05-05 | 2020-11-11 | Regeneron Pharma | Animaux c5 et c3 humanisés |
| NO2785538T3 (fr) | 2014-05-07 | 2018-08-04 | ||
| TW202340452A (zh) | 2015-08-04 | 2023-10-16 | 美商再生元醫藥公司 | 補充牛磺酸之細胞培養基及用法 |
| US20190033329A1 (en) * | 2016-01-25 | 2019-01-31 | President And Fellows Of Harvard College | Methods and compositions for detecting and treating schizophrenia |
| IL309975A (en) | 2016-06-14 | 2024-03-01 | Regeneron Pharma | Antibodies against C5 and their uses |
| EP3504328A1 (fr) | 2016-08-24 | 2019-07-03 | Regeneron Pharmaceuticals, Inc. | Modification de protéines de cellules hôtes |
| CA3054167A1 (fr) | 2017-02-27 | 2018-08-30 | Regeneron Pharmaceuticals, Inc. | Modele humanise de troubles renaux et hepatiques |
| CN110914293B (zh) | 2017-07-06 | 2024-08-13 | 里珍纳龙药品有限公司 | 用于制备糖蛋白的细胞培养工艺 |
| EP3687287B1 (fr) | 2017-09-29 | 2023-07-12 | Regeneron Pharmaceuticals, Inc. | Rongeurs exprimant un complexe c1q humanisé |
| EP3585162B1 (fr) * | 2017-09-29 | 2023-08-30 | Regeneron Pharmaceuticals, Inc. | Rongeurs comprenant un locus ttr humanisé et procédés d'utilisation |
| CN107736281A (zh) * | 2017-09-29 | 2018-02-27 | 中国水产科学研究院珠江水产研究所 | 一种利用益生菌发酵酱油渣防治池塘养殖鳜鱼寄生虫的方法 |
| EP3724226A1 (fr) | 2017-12-13 | 2020-10-21 | Regeneron Pharmaceuticals, Inc. | Associations d'anticorps anti-c5 et utilisations associées |
| AU2018392334A1 (en) | 2017-12-22 | 2020-05-28 | Regeneron Pharmaceuticals, Inc. | System and method for characterizing drug product impurities |
| WO2019152303A1 (fr) | 2018-01-31 | 2019-08-08 | Regeneron Pharmaceuticals, Inc. | Systèmes et procédés permettant de caractériser des impuretés de produit médicamenteux |
| TWI786265B (zh) | 2018-02-02 | 2022-12-11 | 美商再生元醫藥公司 | 用於表徵蛋白質二聚合之系統及方法 |
| AU2019227531A1 (en) | 2018-02-28 | 2020-10-15 | Regeneron Pharmaceuticals, Inc. | Systems and methods for identifying viral contaminants |
| WO2019182901A1 (fr) | 2018-03-19 | 2019-09-26 | Regeneron Pharmaceuticals, Inc. | Dosages et réactifs d'électrophorèse capillaire sur micropuce |
| CA3093356A1 (fr) | 2018-04-03 | 2019-10-10 | Ngm Biopharmaceuticals, Inc. | Agents de liaison a c3 et procedes d'utilisation associes |
| TW202016125A (zh) | 2018-05-10 | 2020-05-01 | 美商再生元醫藥公司 | 用於定量及調節蛋白質黏度之系統與方法 |
| LT3823443T (lt) | 2018-07-16 | 2024-08-12 | Regeneron Pharmaceuticals, Inc. | Ditra ligos graužikų modeliai ir jų naudojimas |
| CN112218877A (zh) | 2018-08-27 | 2021-01-12 | 瑞泽恩制药公司 | 拉曼光谱在下游纯化中的应用 |
| US11754569B2 (en) | 2018-08-30 | 2023-09-12 | Regeneron Pharmaceuticals, Inc. | Methods for characterizing protein complexes |
| CA3111396A1 (fr) * | 2018-09-06 | 2020-03-12 | The Trustees Of The University Of Pennsylvania | Anticorps humanises anti-c5 et leurs utilisations |
| SG11202104237YA (en) | 2019-01-16 | 2021-05-28 | Regeneron Pharma | Methods for identifying free thiols in proteins |
| EP3772929B1 (fr) | 2019-04-04 | 2023-11-15 | Regeneron Pharmaceuticals, Inc. | Rongeurs comprenant un locus facteur 12 de coagulation humanisé |
| BR112021021176A2 (pt) * | 2019-04-24 | 2021-12-28 | Kira Pharmaceuticals Us Llc | Proteína de fusão, métodos para tratar uma doença ou distúrbio mediado pela via do complemento em um indivíduo e para reduzir a atividade de um sistema de complemento de um indivíduo, célula, e, animal não humano geneticamente modificado |
| WO2020231992A1 (fr) | 2019-05-13 | 2020-11-19 | Regeneron Pharmaceuticals, Inc. | Dosages améliorés de liaison de ligands compétitifs |
| WO2020247452A1 (fr) | 2019-06-04 | 2020-12-10 | Regeneron Pharmaceuticals, Inc. | Animaux non humains comprenant un locus ttr humanisé ayant une mutation bêta-slip et procédés d'utilisation |
| WO2020247812A1 (fr) | 2019-06-07 | 2020-12-10 | Regeneron Pharmaceuticals, Inc. | Animaux non humains comprenant un locus d'albumine humanisé |
| US20220323937A1 (en) | 2019-09-24 | 2022-10-13 | Regeneron Pharmaceuticals, Inc. | Systems and methods for chromatography use and regeneration |
| CN114760986A (zh) | 2019-11-25 | 2022-07-15 | 里珍纳龙药品有限公司 | 使用非水性乳液的持续释放调配物 |
| BR122023021668A2 (pt) | 2020-01-21 | 2024-01-09 | Regeneron Pharmaceuticals, Inc. | Método para determinar a estabilidade de uma proteína de interesse |
| MX2023002417A (es) | 2020-08-31 | 2023-03-22 | Regeneron Pharma | Estrategias de suministro de asparagina para mejorar el rendimiento del cultivo celular y mitigar las variantes de secuencia de asparagina. |
| US12082566B2 (en) | 2020-10-01 | 2024-09-10 | Regeneron Pharmaceuticals, Inc. | Rodent animals expressing human CR1 |
| AU2021385363A1 (en) | 2020-11-25 | 2023-06-08 | Regeneron Pharmaceuticals, Inc. | Sustained release formulations using non-aqueous membrane emulsification |
| KR20230121854A (ko) | 2020-12-17 | 2023-08-21 | 리제너론 파아마슈티컬스, 인크. | 단백질-캡슐화 마이크로겔의 제작 |
| TW202233827A (zh) | 2021-01-20 | 2022-09-01 | 美商再生元醫藥公司 | 改良細胞培養中蛋白質效價的方法 |
| US20220404369A1 (en) | 2021-03-03 | 2022-12-22 | Regeneron Pharmaceuticals, Inc. | Systems and methods for quantifying and modifying protein viscosity |
| WO2022204728A1 (fr) | 2021-03-26 | 2022-09-29 | Regeneron Pharmaceuticals, Inc. | Procédés et systèmes pour développer des protocoles de mélange |
| MX2023014246A (es) | 2021-06-01 | 2024-01-17 | Regeneron Pharma | Ensayos y reactivos de microchips de electroforesis capilar. |
| WO2023039457A1 (fr) | 2021-09-08 | 2023-03-16 | Regeneron Pharmaceuticals, Inc. | Procédé à haut rendement et fondé sur la spectrométrie de masse pour quantifier des anticorps et d'autres protéines contenant fc |
| KR20240058201A (ko) | 2021-09-20 | 2024-05-03 | 리제너론 파마슈티칼스 인코포레이티드 | 항체 이질성을 제어하는 방법 |
| AU2022360838A1 (en) | 2021-10-07 | 2024-03-28 | Regeneron Pharmaceuticals, Inc. | Systems and methods of ph modeling and control |
| EP4413359A1 (fr) | 2021-10-07 | 2024-08-14 | Regeneron Pharmaceuticals, Inc. | Étalonnage et correction de ph-mètre |
| WO2023076340A1 (fr) | 2021-10-26 | 2023-05-04 | Regeneron Pharmaceuticals, Inc. | Systèmes et procédés de génération d'eau de laboratoire et de distribution d'eau de laboratoire à différentes températures |
| EP4423271A2 (fr) | 2021-10-28 | 2024-09-04 | Regeneron Pharmaceuticals, Inc. | Procédés et compositions associés à crispr/cas pour la désactivation de c5 |
| AR128824A1 (es) | 2022-03-18 | 2024-06-19 | Regeneron Pharma | Métodos de análisis y cuantificación de variantes polipeptídicas de carga |
| US20240198253A1 (en) | 2022-12-16 | 2024-06-20 | Regeneron Pharmaceuticals, Inc. | Methods and systems for assessing chromatographic column integrity |
| WO2024158961A1 (fr) | 2023-01-25 | 2024-08-02 | Regeneron Pharmaceuticals, Inc. | Caractérisation basée sur la spectrométrie de masse d'anticorps co-exprimés in vivo |
| US20240245779A1 (en) | 2023-01-25 | 2024-07-25 | Regeneron Pharmaceuticals, Inc. | Methods of modeling liquid protein composition stability |
| WO2024178213A2 (fr) | 2023-02-22 | 2024-08-29 | Regeneron Pharmaceuticals, Inc. | Paramètres d'adéquation de système et vieillissement de colonne |
Family Cites Families (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1984003506A1 (fr) | 1983-03-08 | 1984-09-13 | Commw Serum Lab Commission | Sequences d'acides amines antigeniquement actives |
| NZ207394A (en) | 1983-03-08 | 1987-03-06 | Commw Serum Lab Commission | Detecting or determining sequence of amino acids |
| CA1247080A (fr) | 1983-03-08 | 1988-12-20 | Commonwealth Serum Laboratories Commission | Sequences d'acides amines ayant une activite antigenique |
| DE3590766T (fr) | 1985-03-30 | 1987-04-23 | ||
| NZ215865A (en) | 1985-04-22 | 1988-10-28 | Commw Serum Lab Commission | Method of determining the active site of a receptor-binding analogue |
| US5763192A (en) | 1986-11-20 | 1998-06-09 | Ixsys, Incorporated | Process for obtaining DNA, RNA, peptides, polypeptides, or protein, by recombinant DNA technique |
| EP0307434B2 (fr) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Anticorps alteres |
| US5266684A (en) | 1988-05-02 | 1993-11-30 | The Reagents Of The University Of California | Peptide mixtures |
| US5571689A (en) | 1988-06-16 | 1996-11-05 | Washington University | Method of N-acylating peptide and proteins with diheteroatom substituted analogs of myristic acid |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| US5663143A (en) | 1988-09-02 | 1997-09-02 | Dyax Corp. | Engineered human-derived kunitz domains that inhibit human neutrophil elastase |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| US5723286A (en) | 1990-06-20 | 1998-03-03 | Affymax Technologies N.V. | Peptide library and screening systems |
| US5770434A (en) | 1990-09-28 | 1998-06-23 | Ixsys Incorporated | Soluble peptides having constrained, secondary conformation in solution and method of making same |
| US5698426A (en) | 1990-09-28 | 1997-12-16 | Ixsys, Incorporated | Surface expression libraries of heteromeric receptors |
| EP0558671B1 (fr) | 1990-11-21 | 1999-01-27 | Iterex Pharmaceuticals Ltd. Partnership | Synthese de melanges oligomeres multiples equimolaires, notamment de melanges d'oligopeptides |
| ATE164395T1 (de) | 1990-12-03 | 1998-04-15 | Genentech Inc | Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften |
| US5270170A (en) | 1991-10-16 | 1993-12-14 | Affymax Technologies N.V. | Peptide library and screening method |
| US5644048A (en) | 1992-01-10 | 1997-07-01 | Isis Pharmaceuticals, Inc. | Process for preparing phosphorothioate oligonucleotides |
| CA2163345A1 (fr) | 1993-06-16 | 1994-12-22 | Susan Adrienne Morgan | Anticorps |
| US6074642A (en) | 1994-05-02 | 2000-06-13 | Alexion Pharmaceuticals, Inc. | Use of antibodies specific to human complement component C5 for the treatment of glomerulonephritis |
| US6166288A (en) * | 1995-09-27 | 2000-12-26 | Nextran Inc. | Method of producing transgenic animals for xenotransplantation expressing both an enzyme masking or reducing the level of the gal epitope and a complement inhibitor |
| GB9521943D0 (en) | 1995-10-26 | 1996-01-03 | Univ Hertfordshire | Coded particles for process sequence tracking in combinatorial compound library preparation |
| ES2292236T3 (es) | 1998-04-02 | 2008-03-01 | Genentech, Inc. | Variantes de anticuerpos y sus fragmentos. |
| US6335155B1 (en) | 1998-06-26 | 2002-01-01 | Sunesis Pharmaceuticals, Inc. | Methods for rapidly identifying small organic molecule ligands for binding to biological target molecules |
| US6280946B2 (en) | 1998-08-07 | 2001-08-28 | Boston Probes, Inc. | PNA probes, probe sets, methods and kits pertaining to the universal detection of bacteria and eucarya |
| WO2000039585A1 (fr) | 1998-12-28 | 2000-07-06 | Sunesis Pharmaceuticals, Inc. | Identification de ligands de type petites molecules organiques, destines a former des liaisons |
| EP1701611B1 (fr) * | 2003-12-24 | 2011-05-18 | G2 Inflammation Pty Ltd | Mammifere transgenique non humain comprenant un polynucleotide codant pour un recepteur c5ar humain ou humanise |
| JP5137053B2 (ja) | 2004-02-10 | 2013-02-06 | ザ リージェンツ オブ ザ ユニバーシティ オブ コロラド，ア ボディー コーポレイト | 抗ｂ因子抗体もしくはその抗原結合性フラグメント、それを含む組成物、抗原結合性ポリペプチド、および治療薬 |
| CA2827654C (fr) | 2004-10-19 | 2019-04-02 | Regeneron Pharmaceuticals, Inc. | Methode de production d'un animal homozygote pour une modification genetique |
| JP2009523237A (ja) | 2006-01-11 | 2009-06-18 | ノヴォ ノルディスク アクティーゼルスカブ | 改良された球状コード化ビーズ |
| RU2010138612A (ru) * | 2008-02-20 | 2012-03-27 | Джи2 ИНФЛЕММЕЙШН ПТИ ЛТД (AU) | ГУМАНИЗИРОВАННЫЕ АНТИТЕЛА ПРОТИВ C5аR |
| RU2425880C2 (ru) * | 2009-07-30 | 2011-08-10 | Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН | Способ получения трансгенных мышей |
| EP4049535A1 (fr) | 2009-10-06 | 2022-08-31 | Regeneron Pharmaceuticals, Inc. | Souris génétiquement modifiées et greffe |
| PT3375284T (pt) | 2011-02-15 | 2023-06-28 | Univ Yale | Ratinhos humanizados para m-csf e utilizações dos mesmos |
| ES2525368T3 (es) | 2011-10-28 | 2014-12-23 | Regeneron Pharmaceuticals, Inc. | IL-6 y receptor de IL-6 humanizados |
| ES2962287T3 (es) | 2011-10-28 | 2024-03-18 | Regeneron Pharma | Ratones con complejo principal de histocompatibilidad genéticamente modificados |
| US8962913B2 (en) | 2012-06-18 | 2015-02-24 | Regeneron Pharmaceuticals, Inc. | Humanized IL-7 rodents |
| KR20240045263A (ko) | 2012-09-07 | 2024-04-05 | 예일 유니버시티 | 유전적으로 변형된 비-인간 동물 및 이것들의 사용 방법 |
| KR102649893B1 (ko) | 2012-11-05 | 2024-03-25 | 리제너론 파마슈티칼스 인코포레이티드 | 유전자 변형된 비-인간 동물 및 그것의 사용 방법 |
| CN110192541B (zh) | 2013-02-22 | 2022-02-18 | 瑞泽恩制药公司 | 表达人源化主要组织相容性复合物的小鼠 |
| SG11201601828XA (en) | 2013-10-15 | 2016-04-28 | Regeneron Pharma | Humanized il-15 animals |
| KR102173297B1 (ko) | 2013-11-19 | 2020-11-03 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화된 증식-유도 리간드 유전자를 가지고 있는 비-인간 동물 |
| MA51519A (fr) | 2014-05-05 | 2020-11-11 | Regeneron Pharma | Animaux c5 et c3 humanisés |
-
2015
- 2015-05-04 MA MA051519A patent/MA51519A/fr unknown
- 2015-05-04 CN CN201580034127.8A patent/CN106659146B/zh active Active
- 2015-05-04 BR BR112016025751A patent/BR112016025751A2/pt not_active Application Discontinuation
- 2015-05-04 EP EP23202404.2A patent/EP4317445A3/fr active Pending
- 2015-05-04 EP EP15722639.0A patent/EP3142483B1/fr active Active
- 2015-05-04 ES ES19211905T patent/ES2968749T3/es active Active
- 2015-05-04 CA CA2946412A patent/CA2946412C/fr active Active
- 2015-05-04 KR KR1020167032659A patent/KR102461511B1/ko active IP Right Grant
- 2015-05-04 MX MX2016014504A patent/MX2016014504A/es active IP Right Grant
- 2015-05-04 US US14/703,818 patent/US9795121B2/en active Active
- 2015-05-04 EP EP19211905.5A patent/EP3636073B1/fr active Active
- 2015-05-04 RU RU2016146390A patent/RU2713327C2/ru active
- 2015-05-04 SG SG10202003996YA patent/SG10202003996YA/en unknown
- 2015-05-04 WO PCT/US2015/029111 patent/WO2015171523A1/fr active Application Filing
- 2015-05-04 AU AU2015256299A patent/AU2015256299C1/en active Active
- 2015-05-04 SG SG11201608696RA patent/SG11201608696RA/en unknown
- 2015-05-04 JP JP2016566228A patent/JP6598798B2/ja active Active
- 2015-05-04 ES ES15722639T patent/ES2779070T3/es active Active
- 2015-05-04 CA CA3225091A patent/CA3225091A1/fr active Pending
- 2015-05-04 RU RU2020103811A patent/RU2020103811A/ru unknown
-
2016
- 2016-10-25 IL IL248481A patent/IL248481B/en active IP Right Grant
-
2017
- 2017-07-26 US US15/660,833 patent/US10492477B2/en active Active
-
2018
- 2018-07-02 US US16/025,377 patent/US10524458B2/en active Active
-
2019
- 2019-10-21 US US16/658,541 patent/US11178860B2/en active Active
-
2021
- 2021-10-20 US US17/505,834 patent/US20220132818A1/en active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11178860B2 (en) | Humanized C5 animals | |
| US10945418B2 (en) | Genetically modified non-human animal with human or chimeric PD-L1 | |
| US11317611B2 (en) | Genetically modified non-human animal with human or chimeric PD-L1 | |
| US11279948B2 (en) | Genetically modified non-human animal with human or chimeric OX40 | |
| US11505806B2 (en) | Genetically modified non-human animal with human or chimeric OX40 | |
| US11464876B2 (en) | Genetically modified mouse comprising a chimeric TIGIT | |
| AU2018225745B2 (en) | Humanized model of kidney and liver disorders | |
| US20190373868A1 (en) | Genetically modified non-human animal with human or chimeric pd-1 | |
| WO2023046201A1 (fr) | Animal non humain génétiquement modifié comportant des gènes humains ou chimériques |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20231228 |
|
| EEER | Examination request |
Effective date: 20231228 |
|
| EEER | Examination request |
Effective date: 20231228 |
|
| EEER | Examination request |
Effective date: 20231228 |